Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3089849 | Diseases associated with psoriasis in a general population of 159,200 middle-aged, urban, | 1986 | A defined general population of 159,200 male and female native Swedes born in the period of 1911-1940, from an urban catchment area of the then only general hospital, was followed over a decade (1970-1979) with regard to inpatient hospitalization for all kinds of diagnoses. Psoriasis cases (n = 372) are significantly (p less than 0.001) associated with a spectrum of diseases: male as well as female psoriatics seem to show excess rates of viral infections, alcoholism, hypertension, pneumonia, liver cirrhosis, urticaria, and rheumatoid arthritis. Psoriasis in males only seem to be associated with iritis and ankylosing spondylitis, whereas psoriasis in females only is associated with lung cancer, diabetes, obesity, myocardial infarction and asthma. | |
| 3318424 | Endoscopy-controlled study of the safety of nabumetone compared with naproxen in arthritis | 1987 Oct 30 | Nonsteroidal anti-inflammatory drug (NSAID) gastropathy is now a commonly recognized and reported complication of such arthritis therapy. Significant gastric lesions develop in up to 40 percent of arthritic patients treated with long-term anti-inflammatory doses of NSAIDs, 20 percent of which represents actual ulcer crater disease. This 12-week endoscopy-controlled, double-blind study was constructed to evaluate the safety and efficacy of nabumetone 1,000 mg at bedtime compared with naproxen 250 mg twice daily. A total of 37 patients completed the study, including 29 patients with a diagnosis of osteoarthritis and eight with a diagnosis of rheumatoid arthritis. By posttreatment endoscopy, nabumetone was significantly less toxic to the gastrointestinal tract than was naproxen. The nabumetone-treated group also showed greater improvement in all efficacy variables, with significant improvement noted in three of these five variables in both rheumatoid and osteoarthritic patients. | |
| 2666653 | Fibrinopeptide A reactive peptides and procoagulant activity in bronchoalveolar lavage: re | 1989 May | Extravascular, primarily, alveolar fibrin deposition is commonly associated with the alveolitis of many interstitial lung diseases including the interstitial lung disease associated with rheumatoid arthritis (RA). We therefore hypothesized that coagulation pathways, which promote fibrin formation, would be activated in the alveolar lining fluids of patients with rheumatoid interstitial lung disease. To test this hypothesis, we studied the bronchoalveolar lavage (BAL) fluids from patients with rheumatoid interstitial lung disease (n = 7) and patients with RA unassociated with interstitial lung disease (n = 10) to characterize and quantitatively compare the BAL procoagulant material and levels of fibrinopeptide A (FPA), which is cleaved from fibrinogen by thrombin. FPA reactive peptide concentrations were significantly greater in rheumatoid interstitial lung disease than RA when normalized per ml of concentrated BAL fluid (p = 0.02), per mg BAL total protein (p = 0.01) or BAL albumin content (p = 0.03) and correlated with BAL antigenic neutrophil elastase concentrations (r = 0.87). Procoagulant activity was present in similar concentration of BAL of patients with RA and rheumatoid interstitial lung disease and was mainly attributable to tissue factor associated with factor VII (or VIIa). Our results demonstrate that tissue factor and factor VII are endogenous in the alveoli of subjects with RA and interstitial lung disease and could interact with distal coagulation substrates which may enter the alveoli in interstitial lung disease to locally promote fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS) | |
| 3018043 | Very late activation antigens on rheumatoid synovial fluid T lymphocytes. Association with | 1986 Sep | Lymphocytes from the synovial fluid of eight out of eight rheumatoid arthritis (RA) patients had elevated very late activation antigen-1 (VLA-1) expression (10-36% positive cells), whereas peripheral blood lymphocytes (PBL) from RA patients and healthy controls had low VLA-1 expression (0-6% positive cells). During 1-2 wk of in vitro culture, VLA-1 increased on synovial fluid cells but remained low on PBL. In comparison, the interleukin 2 receptor (IL-2 R) was less prominent than VLA-1 on fresh synovial fluid cells, did not increase on cultured synovial fluid T cells, but did increase greatly on cultured PBL. The mitogen PHA reversed or prevented the appearance of VLA-1+, IL-2 R- synovial fluid cells during in vitro culture, thus giving IL-2 R+, VLA-1- cells. These results emphasize that VLA-1+ SF cells are different from resting cells or IL-2 R+ activated PBL T cells, and VLA-1 on synovial fluid T cells may be incompatible with mitogen stimulation. In addition, the VLA-2 heterodimer (165,000/130,000 relative molecular mass [Mr]) was regulated opposite to the VLA-1 heterodimer (130,000/210,000 Mr) on synovial lymphocytes, and thus the VLA-1/VLA-2 ratio is another indicator of the stage of T cell activation. | |
| 3147153 | Antibody levels to mycobacteria in relation to HLA type: evidence for non-HLA-linked high | 1988 Nov | We previously reported DR2 and DR7-associated regulation of antibody binding to mycobacteria in rheumatoid arthritis sera (RA), but not in tuberculosis (Tb). An extensive analysis of antibody to mycobacteria in matched normal sera, in relation to both HLA class I and class II has revealed no class II correlations, confirming that the original findings were due to RA. There was however a very strong association between IgM binding to M. tuberculosis and Cw1 (P = 0.0004). RA patients have strikingly raised levels of IgG (but not of IgA or IgM) binding to the 65 kD heat shock protein of M. tuberculosis, recently implicated in the pathogenesis of adjuvant arthritis in the rat. Remarkably, levels in RA were significantly higher even than in tuberculosis. Levels of this antibody showed no HLA associations. Thus the 65 kD antigen does not account for the DR7, and DR2 associations of IgM and IgA binding to mycobacteria reported previously, but does suggest a role for cross-reactive autoimmunity in RA. | |
| 3458354 | Glucocorticoid receptors in fibroblasts from synovial tissue. Changes during the inflammat | 1986 Mar | There is known to be a significant correlation between the number of glucocorticoid receptors in tissues and their anti-inflammatory effect. In this work, the specific binding of glucocorticoids was studied in inflammatory fibroblasts. Human fibroblasts were obtained from the knee joint of a rheumatoid patient undergoing surgery; experimental fibroblasts were from rat granulomas. The same study was carried out in quiescent synovial fibroblasts from a healthy subject (post-traumatic amputation) and from rat subcutaneous conjunctive tissue. Fibroblasts were obtained by explant cultures and subcultures in monolayers. The stimulation state of cells was evaluated by the amounts of PGE2 and PGF2 alpha released into the culture media. Analysis of the proportions of steroid bound to whole cells showed evidence of specific glucocorticoid receptors in all fibroblasts. Their number was three times higher in cells from inflammatory tissues than from controls. This increased number of receptors in inflammatory cells could be the result of the action of one or more mediators that promote their biosynthesis. | |
| 2525800 | [Efficacy, tolerability and therapeutic benefit of etodolac (Lodine 200) in rheumatologic | 1989 Mar | Efficacy, safety and therapeutic benefit of etodolac (Lodine 200) in rheumatological practice. An open clinical trial performed by 974 rheumatologists enabled an evaluation of efficacy, safety and therapeutic benefit of etodolac (Lodine 200) on 4,947 patients with rheumatoid arthritis, ankylosing spondylitis and osteoarthritis of the lower limbs; the initial dosage was 600 mg/d (for 2 weeks), then 400 to 600 mg/d (for 2 to 4 weeks, according to the indication). Efficacy, assessed by classical items for NSAID's, was shown to be excellent to good by 61-77 p. 100 of patients, according to the indication. 7.7 p. 100 of patients only dropped out for lack of efficacy. 20.4 p. 100 of patients developed adverse effect(s) (AE), but the relationship between etodolac and AE was assessed "possible" or "probable" only for 9.6 p. 100 of patients; this figure should be compared to the 7.6 p. 100 of patients who dropped out for AE and to the 92 p. 100 of patients who assessed the global safety as "excellent or good". The therapeutic benefit was estimated very favorable: 75 p. 100 of patients felt better than at the beginning of the study, 64.5 p. 100 of patients wished to continue the treatment and the (mean) benefit-risk ratio assessed with a logarithm scale (-1 to +1), ranged from 0.45 to 0.6 according to the indication. Therefore, this trial confirmed the good efficacy and safety profile of etodolac on a large scale in normal clinical practice in France, following assessments during controlled trials. It also permitted to perfect new items of evaluation for NSAID's, in particular for therapeutic benefit. | |
| 1899427 | Enhanced production of neutrophil-activating peptide-1/interleukin-8 in rheumatoid arthrit | 1991 Feb | Production of the neutrophil-activating peptide (NAP)-1/IL-8 by mononuclear phagocytes from patients with RA and from control subjects was studied under various conditions. Mononuclear cells from bone marrow (BMMC), PBMC, and synovial fluid (SFMC) were cultured for up to 48 h in the absence or presence of Escherichia coli LPS, different interleukins, interferon-gamma, zymosan, or immune complexes, and the neutrophil-stimulating activity released into the culture medium was determined. As shown by neutralization with an antiserum raised against human recombinant NAP-1/IL-8, over 90% of this activity could be attributed to NAP-1/IL-8. In unstimulated mononuclear cells from control individuals and BMMC from RA patients, the production of NAP-1/IL-8 was very low and was enhanced moderately by stimulation with LPS. By contrast, the spontaneous production of NAP-1/IL-8 was 3- to 10-fold higher in PBMC and even much higher in SFMC from RA patients. In all instances, the yield of NAP-1/IL-8 could be enhanced by stimulation in culture. In addition to LPS, rheumatoid factor-containing immune complexes, zymosan, and IL-1 were highly effective in inducing NAP-1/IL-8 production, while IL-3, GM-CSF, tumor necrosis factor (TNF), and IL-2 were somewhat less potent. An inhibitory effect was obtained with IFN-gamma, which significantly decreased the spontaneous NAP-1/IL-8 release from SFMC and the IL-1- and LPS-induced NAP-1/IL-8 from RA and control PBMC. Inhibition was also observed with glucocorticoids. The production of NAP-1/IL-8 was markedly reduced by dexamethasone in phagocytosis-stimulated PBMC, and almost totally inhibited in SFMC obtained from joints after intraarticular administration of betamethasone. By contrast, the cyclooxygenase inhibitor, indomethacin, tended to increase the NAP-1/IL-8 yield from PBMC in culture. | |
| 2633612 | Methotrexate in rheumatoid arthritis: studies with animal models. | 1989 | The present studies have shown that low doses of methotrexate can suppress the inflammation and joint destruction associated with animal models of arthritis. The antiinflammatory effects of methotrexate are probably related to its inhibitory effect on chemotaxis. At the low doses used, methotrexate does not induce systemic immunosuppression. In methotrexate-treated rats, an improvement in IL-2 synthesis is observed and increases in IL-2 levels are expected to improve cell mediated immunity. Suppressor cells appear to be very sensitive to methotrexate. Macrophage function is modulated by methotrexate. All of these effects including the effects on joint destruction are probably due to inhibition of DHFR activity of critical cells that are involved in the pathogenesis of rat arthritis induced either by adjuvant or by streptococcal cell walls. Some of these effects have been extended to human arthritis but additional studies are required to understand how low dose methotrexate exerts its beneficial effects in humans. | |
| 2347135 | Concentration dependency of cyclosporin and chloroquine as inhibitors of cell proliferatio | 1990 Jan | The effects of the drugs cyclosporin (Cs) and chloroquine (Chl) on the pokeweed mitogen (PWM)-induced immunoglobulin (Ig) production of peripheral blood mononuclear cells (PBMC) of blood donors, were investigated. A significant inhibition of the Ig production was found at concentrations of 0.001-0.025 microgram Cs/ml and 0.1-2.5 microgram Chl/ml of culture medium respectively, while no effect was found on cell proliferation at these concentrations. The combination of various concentrations of Cs with a constant amount of Chl (0.5 microgram/ml) and various concentrations of Chl with a constant amount of Cs (0.005 microgram/ml culture medium), resulted in a reduction of the Ig content in supernatants which was not different from the calculated sum of the effects of the individual drugs at the respective concentrations. It was concluded that both drugs exerted an effect on the PWM-driven stimulation of PBMC, depending on the concentrations used, which might be of interest in the treatment of rheumatoid arthritis. | |
| 3589452 | [Ankylosing panarthritis]. | 1987 Mar | The authors report 4 cases of "Sheathing Panarthritis" (S.P.): two female patients with a positive rheumatoid serology, presented a complete ankylosis of the articular system, including the temporo-mandibular joint and the spine; two male patients presented a complete articular ankylosis of the lower extremities and a more or less total spine ankylosis, by only a slight involvement of the upper extremities. The study of the HLA system, carried out in ten cases--3 in this series--showed the presence of B27 in six cases, and the presence of A2 in five cases out of eight. A single study of locus DR revealed the presence of DR 1. On the nosological point of view, this radio-clinical picture, individualized by Forestier, was successively considered as an autonomous affection, a rheumatoid polyarthritis (P.R.), an ankylosing spondylarthritis (AS). The author's opinion is dual since, from the analysis of the cases, they do not feel that it is possible to classify all cases either with P.R. or with A.S. After studying the various radio-clinical aspects of P.R., they believe that, in patients with S.P., it exists an ankylosing "factor X" which exacerbates the ability of P.R. and A.S. to manufacture sclerosis, transforming these diseases into S.P. | |
| 2903378 | Are antimitochondrial antibodies in primary biliary cirrhosis induced by R(rough)-mutants | 1988 Nov 19 | Antimitochondrial antibody (AMA)-positive serum samples from 45 patients with primary biliary cirrhosis (PBC) and AMA-negative serum samples from patients with chronic liver diseases, systemic lupus erythematosus, or rheumatoid arthritis were studied by an immunoblot technique with mitochondria from bovine heart and pig kidney and with several strains of gram-negative bacteria as antigens after separation by sodiumdodecylsulphate polyacrylamide gel electrophoresis. Serum from patients with PBC recognised up to three mitochondrial antigens with molecular weights of 70 kD, 50 kD, and 42 kD. Equivalent patterns were found with bands at 70-80 kD and 50-52 kD with Enterobacteriaceae as antigens. AMA-reactive polypeptides were localised in the ribosomal and membrane fractions from Enterobacteriaceae but differed from known outer membrane proteins. Conversely, PBC-specific mitochondrial antigens at 70 kD and 50 kD were recognised by rabbit antisera against Salmonella minnesota Rb and Rc mutants but not by antisera against wild-type Enterobacteriaceae. Absorption experiments and two-dimensional immunoblotting studies confirmed that mitochondria and gram-negative bacteria share identical PBC-specific determinants. It seems that PBC-specific antigens are expressed in gram-negative bacteria and that these antigens may be immunogenic in mutants with defective polysaccharide synthesis. The data support the hypothesis of a bacterial aetiology for PBC. | |
| 3276492 | [Immunomodulating therapy in chronic polyarthritis with thymopentin. A multicenter placebo | 1988 Feb 5 | In a multicenter, placebo-controlled and randomized double-blind trial 119 patients with rheumatoid arthritis were treated with thymopentin, an immunoregulating drug. The data of 107 patients were complete enough to be evaluated: 51 were given intravenous injections over ten minutes of 50 mg thymopentin three times weekly, 56 were similarly treated with a placebo solution. Significant improvement of five among nine clinical criteria were obtained with thymopentin after the third week of treatment. The response rate (improvement of a clinical parameter by at least 40%) was significantly greater for all clinical parameters in the thymopentin group. Regression to a functionally more favourable class (Steinbrocker's classification) occurred in seven thymopentin-treated, but in none of the placebo-treated patients. The improvement gradually subsided over four weeks after the end of treatment. There were no changes during the trial with respect to immunological, biochemical or haematological findings. Except for one systemic allergic reaction there were no side effects. | |
| 1893621 | Anti-IL-1 alpha autoantibodies in patients with rheumatic diseases and in healthy subjects | 1991 Sep | We have developed a quantitative assay for IgG autoantibodies against IL-1 alpha using protein A-Sepharose CL-4B. We examined the autoantibodies in sera from 107 healthy subjects, 151 patients with rheumatoid arthritis (RA), 64 patients with systemic lupus erythematosus (SLE) and 16 patients with systemic sclerosis. The frequency of positive sera for the autoantibodies in patients with RA was 16.6%, which was about three times more frequent (P less than 0.01) than that in healthy subjects (5.6%) or that in patients with SLE (4.7%). Only one serum of 16 patients with systemic sclerosis was positive for the autoantibodies. Neutralizing activity of the autoantibodies was demonstrated by murine thymocyte proliferation assay. The concentrations of IgG at 50% inhibition of IL-1 alpha (15 pM) induced thymocyte proliferation ranged between 0.1 and 0.5 mg/ml. A time-course study showed fluctuations of the titres of the autoantibodies in parallel with the disease activity of RA. These results suggest that the anti-IL-1 alpha autoantibodies present in the sera and possibly some other body fluids may be involved in the regulation of IL-1 activity in vivo. | |
| 2746583 | Estimates of the prevalence of selected arthritic and musculoskeletal diseases in the Unit | 1989 Apr | The National Arthritis Data Workgroup focused its studies primarily on joint disease with the addition of osteoporosis which is a frequently occurring musculoskeletal condition and public health problem. We used national data sets as well as published studies to estimate prevalence in the United States. We report on prevalence rather than incidence because of the difficulty in defining the point of onset and because primary national data sources currently available are concerned with disease prevalence. | |
| 3536250 | The synthetic processes of articular cartilage. | 1986 Dec | The cells of cartilage are constantly remodeling the matrix in which they are suspended. The stimulus to initiate remodeling is probably the chondrocyte's response to physical and or chemical changes in the environment. Heat, pressure, friction, load, pH, and growth are examples of such factors, which, if altered, would have a dramatic effect on the cell's state of health. The mode of response by the chondrocyte is specific for a given stimulus. Elevated temperature, for example, switches on a set of genes, the heat shock genes, in chondrocytes. This results in the synthesis of a series of cellular protein that presumably in turn protects the cell from the injurious effects of heat. Load and pressure affect both the synthetic rate of matrix protein and the degradation rates of preexisting matrix. A number of low-molecular-weight proteins appear to be involved in anabolic and catabolic processes of cartilage. A protein recently isolated from synovium stimulates the synthesis of degradative enzymes in cartilage. This factor is probably involved in the remodeling process under normal physiologic conditions. More recently, it has been found in elevated levels under pathologic conditions such as in the synovial fluid of patients with rheumatoid and osteoarthritis. The mechanism by which this factor turns on the degradative pathway appears complex and is under investigation. | |
| 2508357 | [Prostaglandin E2, interleukin 1 and gamma interferon production of mononuclear cells of p | 1989 Jul | Inflammatory joint diseases exhibit distinct pathohistological and immunological characteristics. The studies performed demonstrated that in comparison to normal controls peripheral blood mononuclear cells from patients with rheumatoid arthritis (RA) presented an increased percentage of monocytic cells. Peripheral blood mononuclear cells from patients with RA produced significantly increased amounts of prostaglandin E2 and significantly decreased amounts of interferon-gamma following mitogen stimulation with LPS or PWM respectively. The spontaneous production of interleukin 1 was found to be elevated. A significantly increased LPS induced production of prostaglandin E2 could also be observed in monocyte depleted rheumatoid peripheral cells and in peripheral cells of patients with osteoarthritis and HLAB27 associated joint diseases. Mononuclear cells from rheumatoid synovial tissue produced increased amounts of prostaglandin E2 and decreased amounts of interferon-gamma; the spontaneous prostaglandin E2 production was similar to the values obtained by mitogen stimulation which may originate from the distinct cellular composition of synovial tissue. | |
| 2055095 | Stress proteins, autoimmunity, and autoimmune disease. | 1991 | At birth, the immune system is biased toward recognition of microbial antigens in order to protect the host from infection. Recent data suggest that an important initial line of defense in this regard involves autologous stress proteins, especially conserved peptides of hsp60, which are presented to T cells bearing gamma delta receptors by relatively nonpolymorphic class lb molecules. Natural antibodies may represent a parallel B cell mechanism. Through an evolving process of "physiological" autoreactivity and selection by immunodominant stress proteins common to all prokaryotes, B and T cell repertoires expand during life to meet the continuing challenge of infection. Because stress proteins of bacteria are homologous with stress proteins of the host, there exists in genetically susceptible individuals a constant risk of autoimmune disease due to failure of mechanisms for self-nonself discrimination. That stress proteins actually play a role in autoimmune processes is supported by a growing body of evidence which, collectively, suggests that autoreactivity in chronic inflammatory arthritis involves, at least initially, gamma delta cells which recognize epitopes of the stress protein hsp60. Alternate mechanisms for T cell stimulation by stress proteins undoubtedly also exist, e.g., molecular mimicry of the DR beta third hypervariable region susceptibility locus for rheumatoid arthritis by a DnaJ stress protein epitope in gram-negative bacteria. While there still is confusion with respect to the most relevant stress protein epitopes, a central role for stress proteins in the etiology of arthritis appears likely. Furthermore, insight derived from the work thus far in adjuvant-induced arthritis already is stimulating analyses of related phenomena in autoimmune diseases other than those involving joints. Only limited data are available in the area of humoral autoimmunity to stress proteins. Autoantibodies to a number of stress proteins have been identified in SLE and rheumatoid arthritis, but their pathogenetic significance remains to be established. Nevertheless, the capacity of certain stress proteins to bind to multiple proteins in the nucleus and cytoplasm both physiologically and during stress or injury to cells, suggests that stress proteins may be important elements in the "immunogenic particle" concept of the origin of antinuclear and other autoantibodies. In short, this fascinating group of proteins, so mysterious only a few years ago, has impelled truly extraordinary new lines of investigation into the nature of autoimmunity and autoimmune disease. | |
| 1863821 | Evidence for impaired erythropoietin response to anaemia in rheumatoid disease. | 1991 Aug | In this study we determined the serum erythropoietin (Epo) levels of 97 anaemic rheumatoid (RD) patients (Hb less than 11 g/dl) of whom 44 had serum ferritin greater than 60 micrograms/l (anaemia of chronic disorders; ACD), 26 had ferritin 20-60 micrograms/l and 27 had ferritin less than 20 micrograms/l. These results were compared with the Epo levels of 36 iron deficient controls (Hb less than 11 g/dl), 33 non-anaemic RD patients and 33 normals. The serum Epo levels of anaemic subjects were significantly higher (P less than 0.05) than those of non-anaemic patients. Despite similar Hb, the Epo results (geometric mean (confidence limits] of the ACD group (38 (32,45) mU/ml) and of RD patients with ferritin of 20-60 micrograms/l (39 (33,46)mU/ml) were significantly lower (P less than 0.05) than those of iron deficient controls (65 (52,80)mU/ml). When the Hb fell to 10 g/dl or less, the serum Epo of 13 RD patients with ferritin less than 20 micrograms/l was 65 (47,89)mU/ml, significantly lower (P less than 0.05) than that of 17 iron deficient controls (104 (78,136)mU/ml). These results justify clinical trials of recombinant human Epo in RD patients with ACD. | |
| 2680316 | Meta-analysis of grip strength: most common, but superfluous variable in comparative NSAID | 1989 Oct | A meta-analysis was done on grip strength, the most common variable in comparative NSAID trials. The median grip strength was 133 mm Hg (SD 64). The drugs were better than placebo (11.9 mm Hg, confidence interval (CI): 8.9-14.9), but the full dose was not significantly superior to half the dose (3.5 mm Hg, CI: -1.4 to +8.4 mm Hg). The difference between new drugs and control drugs in 70 crossover trials was only 1.4 mm Hg (CI: -0.1 to +2.9). Significant results in favour of the new drug were claimed more often than expected (p less than 0.01), suggesting biased data analysis. Grip strength is a superfluous variable in comparative NSAID trials: even the drug effect over placebo was less than what most rheumatologists considered of relevance. |